# PATHOGENESIS AND THERAPY OF SYSTEMIC LUPUS ERYTHEMATOSUS

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 1991 · $219,823

## Abstract

DESCRIPTION (adapted from applicant's abstract):  Lupus nephritis is caused
by pathogenic autoantibodies (Abs) that are T-cell dependent.  In NZB/NZW
Fl (BW) mice, and in patients, some Abs deposited in glomeruli bear a
public Id designated 1d6N2.  The investigators hypothesize that B-cells
producing Ids enriched in pathogens are upregulated by helper T-cells (TH)
which are activated by complementary Id structures.  The investigators
developed and are characterizing BW monoclonal (Mab) Abs to dsDNA with
regard to pathogenicity (in vitro), isotype, charge, complement- fixing
abilities, epitope specificity, and Id expression.  Four are 1dGN2+ 1gG2a
high avidity anti-dsDNA; two accelerate nephritis in young BWs, two do not.
Several BW L3T4+, Ly2-TH have been cloned and are being characterized for
MHC restriction, proliferative responses to DNA, Id and anti-Ids,
lymphokine profiles, ability to regulate production of various lds by
unprimed BW B-cells in vitro, and ability to alter Ids, anti-Ids and
disease in vitro.  Two TH (Mosmann Class 2) cells that upreguate production
of 1dGN2 accelerate nephritis; one TH (Mosmann 1) does not upregulate 1dGN2
or accelerate disease.  Based on these observations, the investigators
propose three studies.  1) Define the structures which determine expression
of various public Ids on V regions of Ig molecules, by sequencing of H and
L chain V regions, modeling the Ag-binding groove, and developing mutant H
and/or L chains to separate Id expression and Ag-binding.  Correlations
will be made between pathogenicity and differences in structure, Id,
epitope specificity, etc.  2) Define the structures recognized by IdTH,
most likely peptides presented by MHC on B-cells.  Synthetic peptides will
be used to stimulate TH and to inhibit in vitro interactions between BW B
and IdTH.  Wild and mutant Ig molecules will also be presented to IdTH by
B-cells to determine the structure of Ids recognized by TH.  3) Based on
results of 1 and 2, the investigators will test interventions designed to
inactivate various IdTH that support production of pathogenic Abs. Two
approaches will be used - Mabs against TcR of IdTH, and tolerization with
peptides.  The overall objective is to understand a mechanism contributing
to disease and develop interventions that result in specific suppression of
pathogenic Ab subsets.

## Key facts

- **NIH application ID:** 3156702
- **Project number:** 5R01AR033962-07
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **SAM.gov UEI:** RN64EPNH8JC6
- **Principal Investigator:** BEVRA H HAHN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $219,823
- **Award type:** 5
- **Project period:** 1983-09-01 → 1994-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3156702

## Citation

> US National Institutes of Health, RePORTER application 3156702, PATHOGENESIS AND THERAPY OF SYSTEMIC LUPUS ERYTHEMATOSUS (5R01AR033962-07). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3156702. Licensed CC0.

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